Role of Dynamics and Mutations in Interactions of a Zinc Finger Antiviral Protein with CG-rich Viral RNA

核糖核酸 锌指 生物 RNA沉默 RNA结合蛋白 抗病毒蛋白 生物物理学 细胞生物学 化学 分子生物学 遗传学 基因 转录因子 RNA干扰
作者
Saikat Pal,Amit Kumar,Harish Vashisth
出处
期刊:Journal of Chemical Information and Modeling [American Chemical Society]
卷期号:63 (3): 1002-1011 被引量:2
标识
DOI:10.1021/acs.jcim.2c01487
摘要

Zinc finger antiviral protein (ZAP) is a host antiviral factor that selectively inhibits the replication of a variety of viruses. ZAP recognizes the CG-enriched RNA sequences and activates the viral RNA degradation machinery. In this work, we investigated the dynamics of a ZAP/RNA complex and computed the energetics of mutations in ZAP that affect its binding to the viral RNA. The crystal structure of a mouse-ZAP/RNA complex showed that RNA interacts with the zinc finger 2 (ZF2) and ZF3 domains. However, we found that due to the dynamic behavior of the single-stranded RNA, the terminal nucleotides C1 and G2 of RNA change their positions from the ZF3 to the ZF1 domain. Moreover, the electrostatic interactions between the zinc ions and the viral RNA provide further stability to the ZAP/RNA complex. We also provide structural and thermodynamic evidence for seven residue pairs (C1-Arg74, C1-Arg179, G2-Arg74, U3-Lys76, C4-Lys76, G5-Arg95, and U6-Glu204) that show favorable ZAP/RNA interactions, although these interactions were not observed in the ZAP/RNA crystal structure. Consistent with the observations from the mouse-ZAP/RNA crystal structure, we found that four residue pairs (C4-Lys89, C4-Leu90, C4-Tyr108, and G5-Lys107) maintained stable interactions in MD simulations. Based on experimental mutagenesis studies and our residue-level interaction analysis, we chose seven residues (Arg74, Lys76, Lys89, Arg95, Lys107, Tyr108, and Arg179) for individual alanine mutations. In addition, we studied mutations in those residues that are only observed in the crystal structures as interacting with RNA (Tyr98, Glu148, and Arg170). Out of these 10 mutations, we found that the Ala mutation in each of the five residues Arg74, Lys76, Lys89, Lys107, and Glu148 significantly reduced the binding affinity of ZAP to RNA.
最长约 10秒,即可获得该文献文件

科研通智能强力驱动
Strongly Powered by AbleSci AI
更新
PDF的下载单位、IP信息已删除 (2025-6-4)

科研通是完全免费的文献互助平台,具备全网最快的应助速度,最高的求助完成率。 对每一个文献求助,科研通都将尽心尽力,给求助人一个满意的交代。
实时播报
Distance发布了新的文献求助10
1秒前
2秒前
2秒前
专注灵凡完成签到,获得积分10
2秒前
Stageruner完成签到,获得积分10
2秒前
kiyo_v完成签到,获得积分10
2秒前
黄超超发布了新的文献求助10
3秒前
落寞剑成完成签到 ,获得积分10
3秒前
七子完成签到,获得积分10
3秒前
klio完成签到 ,获得积分10
4秒前
zzx396完成签到,获得积分0
5秒前
one完成签到 ,获得积分10
6秒前
十五完成签到,获得积分10
6秒前
ptjam完成签到 ,获得积分10
7秒前
神勇的晟睿完成签到 ,获得积分10
8秒前
8秒前
曾珍完成签到 ,获得积分10
8秒前
Muhi完成签到,获得积分10
8秒前
8秒前
自带蓝牙的土豆完成签到 ,获得积分10
9秒前
青羽落霞完成签到 ,获得积分10
10秒前
抹颜完成签到,获得积分10
11秒前
量子星尘发布了新的文献求助10
15秒前
胡图图完成签到,获得积分10
16秒前
睡觉大王完成签到 ,获得积分10
17秒前
18秒前
18秒前
19秒前
19秒前
24秒前
玩命的十三完成签到 ,获得积分10
24秒前
寂寞的诗云完成签到,获得积分10
26秒前
我爱科研完成签到 ,获得积分10
26秒前
27秒前
Bin_Liu发布了新的文献求助10
28秒前
She完成签到,获得积分10
28秒前
31秒前
Raki完成签到,获得积分10
32秒前
22完成签到 ,获得积分10
32秒前
Echo_1995完成签到,获得积分10
35秒前
高分求助中
【提示信息,请勿应助】关于scihub 10000
Les Mantodea de Guyane: Insecta, Polyneoptera [The Mantids of French Guiana] 3000
徐淮辽南地区新元古代叠层石及生物地层 3000
The Mother of All Tableaux: Order, Equivalence, and Geometry in the Large-scale Structure of Optimality Theory 3000
Handbook of Industrial Diamonds.Vol2 1100
Global Eyelash Assessment scale (GEA) 1000
Picture Books with Same-sex Parented Families: Unintentional Censorship 550
热门求助领域 (近24小时)
化学 材料科学 医学 生物 工程类 有机化学 生物化学 物理 内科学 纳米技术 计算机科学 化学工程 复合材料 遗传学 基因 物理化学 催化作用 冶金 细胞生物学 免疫学
热门帖子
关注 科研通微信公众号,转发送积分 4038184
求助须知:如何正确求助?哪些是违规求助? 3575908
关于积分的说明 11373872
捐赠科研通 3305715
什么是DOI,文献DOI怎么找? 1819255
邀请新用户注册赠送积分活动 892662
科研通“疑难数据库(出版商)”最低求助积分说明 815022